Tardif M, Beauchamp D, Bergeron Y, Lessard C, Gourde P, Bergeron M G
Laboratoire et Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
Antimicrob Agents Chemother. 1994 Jul;38(7):1555-60. doi: 10.1128/AAC.38.7.1555.
In this study, the relationship between leukotrienes, peritubular cell infiltration with polymorphonuclear cells (PMNs) and renal tubular damage was investigated in a rat model of acute ascending pyelonephritis. Infection was induced by the injection of 10(5) CFU of Escherichia coli into the bladder and occlusion of the left ureter for 24 h. Treatment of infected animals was started 24 h after the induction of pyelonephritis with either hydrocortisone (25 mg/kg of body weight per day), the leukotriene inhibitor L-651,392 (10 mg/kg/day), or the vehicle of L-651,392 and was maintained for 5 days. At the end of treatment, the animals were killed, serum was collected, and both kidneys were removed for colony counts and histopathology. Renal function was evaluated by the measurement of blood urea nitrogen levels and creatinine clearance. The numbers of PMNs and mononuclear cells (MNs) in the cortex and medulla were recorded for all groups on plastic sections done from the left kidney. Infection alone (vehicle of L-651,392) resulted in intensive interstitial infiltration and a severe tubular destruction in the cortex. Treatment with hydrocortisone did not prevent PMN migration and tissue damage. By contrast, treatment with L-651,392 resulted in a significant reduction in PMNs (P < 0.001 in comparisons with all other groups) and greater preservation of the tubular structure despite identical bacterial counts than in the group receiving hydrocortisone. We conclude that L-651,392 prevents inflammatory cells from reaching the site of infection and protects the kidney from tubular damage associated with inflammation during pyelonephritis. Inhibitors of leukotrienes should be further investigated for their potential benefit as adjuvants to antibiotherapy in the treatment of pyelonephritis.
在本研究中，我们在急性上行性肾盂肾炎大鼠模型中研究了白三烯、肾小管周围多形核细胞（PMN）浸润与肾小管损伤之间的关系。通过向膀胱内注射10⁵CFU大肠杆菌并结扎左侧输尿管24小时诱导感染。肾盂肾炎诱导24小时后，开始对感染动物进行治疗，分别给予氢化可的松（25mg/kg体重/天）、白三烯抑制剂L-651,392（10mg/kg/天）或L-651,392的溶剂，并持续治疗5天。治疗结束时，处死动物，收集血清，并取出双侧肾脏进行菌落计数和组织病理学检查。通过测量血尿素氮水平和肌酐清除率评估肾功能。对左侧肾脏制作的塑料切片上所有组的皮质和髓质中的PMN和单核细胞（MN）数量进行记录。单独感染（L-651,392的溶剂）导致皮质内密集的间质浸润和严重的肾小管破坏。氢化可的松治疗不能阻止PMN迁移和组织损伤。相比之下，L-651,392治疗导致PMN显著减少（与所有其他组相比，P<0.001），尽管细菌计数相同，但与接受氢化可的松治疗的组相比，肾小管结构得到了更好的保存。我们得出结论，L-651,392可阻止炎症细胞到达感染部位，并保护肾脏免受肾盂肾炎期间与炎症相关的肾小管损伤。白三烯抑制剂作为肾盂肾炎抗菌治疗辅助药物的潜在益处应进一步研究。
